This revised application is designed to continue and expand the training program in mental retardation and developmental disabilities (MRDD) at Mount Sinai School of Medicine. This program has been developed to provide a combined basic science and clinical background in the etiology, pathophysiology, prevention, and treatment of genetic diseases leading to MRDD. The training is primarily in the fields of genetics and neurobiology as related to MRDD. The specific subdisciplines include molecular and biochemical genetics, developmental neurobiology, neurogenetics, cytogenetics, and clinical genetics. Three major research themes of this program are: 1) elucidation of the basic molecular etiologies of genetic disorders resulting in MRDD, 2) application of molecular genetic and cell biologic techniques to investigate the basic biology and pathogenesis of these disorders, and 3) development and evaluation of molecular-based therapies for inherited diseases. There is interdisciplinary input which has been enhanced by the addition of outstanding faculty in molecular biology, neurobiology, cell biology, bioinformatics, and gene therapy, areas of recent institutional growth and expansion. Postdoctoral Ph.D. trainees will be primarily involved in research, while those with M.D. degrees also will participate in a clinical training component designed for exposure and experience in the diagnosis, management, and treatment of patients with MRDD of diverse etiologies. Predoctoral trainees will receive didactic training in human genetics, molecular/cellular biology, neurobiology, and mental retardation. Emphasis will be placed on rigorous research training with thesis dissertations in human genetics focused on specific problems in MRDD. All trainees will attend an annual retreat designed to provide a broad overview of MRDD and to highlight the latest advances, particularly as related to their genetic etiology, prevention, and treatment. All trainees also will attend the MRDD monthly seminar series. Highly qualified trainees will be selected from a national pool and special emphasis will be directed to recruit women and underrepresented minorities. Internal and External Advisory Committees will review progress and advise the Program Directors on new directions and programmatic, trainee, and administrative issues. In addition, the proposed program will imbue trainees with the principles of integrity in the conduct of research. It is anticipated that these trainees will continue the tradition of this program by becoming basic and/or clinical researchers in the field of human genetics and mental retardation. [unreadable] [unreadable]